tbuckley/cabot-search huggingface dataset:
PD-1 blockade with sintilimab plus induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) versus IC-CCRT in locoregionally-advanced nasopharyngeal carcinoma (LANPC): A multicenter, phase 3, randomized controlled trial (CONTINUUM).
Authors: Jun Ma, Ying Sun, Xu Liu, Kun-Yu Yang, Ning Zhang, Feng Jin, Guorong Zou, Xiaodong Zhu, Fangyun Xie, Zhenyu He, Nian-Yong Chen, Yan-Ping Mao, Liangfang Shen, Mei Shi, Shu-Bin Hong, Hongyun Zhao, Ji-Bin Li, Ling-Long Tang, Na Liu, Yu-Pei Chen
Journal: Journal of Clinical Oncology (2023)

LBA6002 Background: Despite the success of PD-1 blockade plus chemotherapy in recurrent/metastatic NPC, its role in LANPC is unproven. This trial evaluated the efficacy and safety of adding sintilimab (a PD-1 inhibitor) to IC-CCRT in LANPC. Methods: Patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0/T3N1) were enrolled at 9 centers in China, and randomized (1:1; stratified by center and stage with block size four) to the Standard Arm (gemcitabine and cisplatin IC plus cisplatin CCRT), or Sintilimab Arm (sintilimab plus IC-CCRT). Sintilimab 200mg was given intravenously once every 3 weeks for up to 12 cycles (3 induction, 3 concurrent, and 6 adjuvant). The primary endpoint was event-free survival (EFS) (i.e. freedom from local/regional/distant failure or death). It is estimated that approximately 417 patients would provide 80% power to detect a hazard ratio (HR) of 0.52 with a two-sided type 1 error of 0.05. Quality of life (QoL) was assessed by EORTC-C30. Biomarkers including tertiary lymphoid structure (TLS), PD-L1, and gene expression were also analyzed. Results: Between December 2018, and March 2020, 425 patients were randomized to the Sintilimab Arm (n = 210) and Standard Arm (n = 215). After a median follow-up of 42 months (94% alive patients ≥36 months), the intention-to-treat analysis showed that 3-year EFS was 86.1% in the Sintilimab Arm and 76.0% in the Standard Arm (stratified HR, 0.59; 95% confidence interval [CI], 0.38-0.92; stratified log-rank p = 0.019). Grade 3-4 adverse events (AEs) occurred in 155 (74.2%) and 140 (65.4%) patients, including immune-related AEs in 20 (9.6%) and 2 (0.9%) patients and grade 5 AEs in 2 (0.95%) and 1 (0.5%) patients in the Sintilimab and Standard Arm, respectively (Table). No minimum clinically important differences in QoL were observed. The benefit of the addition of sintilimab was observed in patients with TLS (HR 0.18; 95% CI, 0.04-0.81; p = 0.011) but not in patients without TLS (HR 0.94; 95% CI, 0.50-1.76; p = 0.85). Conclusions: The addition of sintilimab to standard IC-CCRT results in significant improvement of EFS, manageable safety profile, and comparable QoL in high-risk LANPC. TLS appears to be a predictive biomarker for benefit of sintilimab. Clinical trial information: NCT03700476 . [Table: see text]
Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results.
Authors: Funda Meric-Bernstam, Vicky Makker, Ana Oaknin, Do-Youn Oh, Susana N. Banerjee, Antonio Gonzalez Martin, Kyung Hae Jung, Iwona A. Lugowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Chiedozie Anoka, Yan Ma, Soham D. Puvvada, Jung-Yun Lee
Journal: Journal of Clinical Oncology (2023)

LBA3000 Background: T-DXd is an antibody drug conjugate targeting HER2 and is approved in HER2-expressing breast (BC) and gastric (GC) cancers. HER2 expression is prevalent in other solid tumors. The efficacy of current treatments (Tx) in these populations, including studies with HER2-directed Tx, is modest, revealing a significant unmet medical need. Clinically meaningful activity of T-DXd was seen in HER2-expressing tumors in a phase 1 study (NCT02564900). Methods: DP-02 (NCT04482309) is an open-label phase 2 study of T-DXd 5.4 mg/kg q3w in pts with HER2-expressing (immunohistochemistry [IHC] 3+ or IHC 2+ by local or central testing) locally advanced or metastatic disease that progressed after ≥1 systemic Tx or that has no Tx options. Cohorts with biliary tract (BTC), bladder (URO), cervical (CC), endometrial (EC), ovarian (OC), pancreatic (PC), or other tumors (excluding BC, GC, colorectal cancer, and non-small cell lung cancer) were enrolled. Efficacy and safety were analyzed in all pts who received ≥1 dose of T-DXd. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate, progression-free and overall survival, and safety. Results: At data cutoff (16 Nov 2022; median follow-up, 9.7 mo), 267 pts had been treated (median, 2 prior lines of Tx [range, 0-13]); 75 pts were IHC 3+ and 125 were IHC 2+ by central testing. In all 267 pts, the ORR was 37.1% and median DOR (mDOR) was 11.8 mo; in pts with IHC 3+ expression, the ORR was 61.3% and mDOR was 22.1 mo. ORR per cohort is shown in all pts and those with centrally confirmed HER2 IHC 3+ or IHC 2+ expression. Grade (G) ≥3 adverse events (AEs) occurred in 58.4% of pts; 11.6% discontinued Tx due to AEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 18 pts (6.7% [G1, n=6; G2, n=11; G5, n=1]). Conclusions: This is the first tumor-agnostic global study of T-DXd in a broad range of HER2-expressing solid tumors. T-DXd showed encouraging ORR, particularly in pts with IHC 3+ expression, durable clinical benefit, and a manageable safety profile in this heavily pretreated population. These interim results show T-DXd to be a potential new Tx option for pts with HER2-expressing solid tumors. Clinical trial information: NCT04482309 . [Table: see text]
Nine-weeks versus one-year trastuzumab for early-stage HER2+ breast cancer: 10-year update of the Short-HER phase III randomized trial.
Authors: Pier Franco Conte, Giancarlo Bisagni, Federico Piacentini, Samanta Sarti, Santino Minichillo, Elisa Anselmi, Michele Aieta, Vittorio Gebbia, A Schirone, Antonino Musolino, Ornelia Garrone, A Beano, Anita Rimanti, Francesco Giotta, Anna Turletti, Maria Vittoria Dieci, Roberto Vicini, Sara Balduzzi, R D'Amico, Valentina Guarneri
Journal: Journal of Clinical Oncology (2023)

LBA637 Background: The ShortHER trial is a phase III non-inferiority, randomized trial comparing 9 weeks (short arm) versus 1 year (long arm) of adjuvant trastuzumab combined with chemotherapy in HER2+ eBC patients. The first primary end point of the study was the event-driven analysis of disease-free survival which was achieved in 2017, presented at ASCO 2017 and published in Annals of Oncology in 2018. The HR was 1.13 (90% CI 0.89-1.42) and the non-inferiority could not be claimed as the upper border of CI crossed the upper limit of 1.29 chosen as non-inferiority margin. According to a pre-planned Bayesian analysis, the probability that the short arm was not inferior to the standard one was 80%. Methods: 1254 HER2+ early breast cancer patients were stratified according to nodal status and randomized. Median age was 55 years (range 25-78); 672 (54%) patients were node negative, 383 (30%) with 1-3 positive nodes, 198 (16%) 4 or more positive nodes. At the time of the event-driven analysis, median follow up was 6 years, 200 DFS events and 78 deaths were reported. Here we report the overall survival,+ which was the second co-primary end point, updated DFS and outcomes according to nodal status. Results: Median follow-up is now 9 years, 248 DFS events and 116 deaths have been reported. The 10 year DFS is 77% in the long arm and 78% in the short arm (HR 1.06; 90% CI 0.86-1.31). The 10-year OS is 89% in the long arm and 88% in the short arm (HR 1.15; 90% CI 0.85-1.56). The DFS and OS data overall and by nodal status are summarized in the table below. Conclusions: At a median follow-up of 9 years, the ShortHER trial shows that 1 year trastuzumab is still the standard treatment for HER2+ eBC patients as non-inferiority cannot be claimed in terms of DFS or OS. Numerically however, the differences for the patients at low risk (N0) or intermediate risk (N 1-3) is negligible and patients with 4 or more positive lymph nodes have a clear benefit with 1 year trastuzumab. I. This long-term date can reassure clinicians if, for any reason a patient at low/intermediate risk has to stop trastuzumab and, more important, might facilitate access to a far less expensive treatment to the thousands of patients worldwide who cannot afford the cost of one year of trastuzumab. Clinical trial information: NCT00629278 . [Table: see text]
Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia
Authors: Yunpeng Liu-Lupo, James Dongjoo Ham, Swarna K. A. Jeewajee, Lan Nguyen, Toni Delorey, Azucena Ramos, David M. Weinstock, Aviv Regev, Michael T. Hemann
Journal: Blood Cancer Journal (2023)

Abstract Whole chromosome losses resulting in near-haploid karyotypes are found in a rare subgroup of treatment-refractory acute lymphoblastic leukemia. To systematically dissect the unique physiology and uncover susceptibilities that can be exploited in near-haploid leukemia, we leveraged single-cell RNA-Seq and computational inference of cell cycle stages to pinpoint key differences between near-haploid and diploid leukemia cells. Combining cell cycle stage-specific differential expression with gene essentiality scores from a genome-wide CRISPR-Cas9-mediated knockout screen, we identified the homologous recombination pathway component RAD51B as an essential gene in near-haploid leukemia. DNA damage analyses revealed significantly increased sensitivity of RAD51-mediated repair to RAD51B loss in the G2/M stage of near-haploid cells, suggesting a unique role of RAD51B in the homologous recombination pathway. Elevated G2/M and G1/S checkpoint signaling was part of a RAD51B signature expression program in response to chemotherapy in a xenograft model of human near-haploid B-ALL, and RAD51B and its associated programs were overexpressed in a large panel of near-haploid B-ALL patients. These data highlight a unique genetic dependency on DNA repair machinery in near-haploid leukemia and demarcate RAD51B as a promising candidate for targeted therapy in this treatment-resistant disease.
First-in-human study of ZG19018, targeting KRAS G12C, as monotherapy in patients with advanced solid tumors.
Authors: Rongrui Liu, Xiujuan Qu, Nong Yang, Xiaoli Chai, Jianming Xu
Journal: Journal of Clinical Oncology (2023)

e15127 Background: ZG19018 tablet is a selective KRAS G12C inhibitor that inhibits the activation of KRAS G12C and multiple downstream signaling pathways. It showed very promising anti-tumor effects in preclinical studies. Here we report the preliminary results from a phase 1 dose escalation study that assessed the tolerability, safety, pharmacokinetics and efficacy of ZG19018 in patients (pts) with advanced solid tumors. Methods: This is an open-label, multi-center study in pts with KRAS G12C mutated solid tumors and progressed following prior standard therapies. The study consisted of a rapid dose-escalation phase for the low-dose groups (50 mg qd and 150 mg qd, orally) and a standard 3+3 design phase for the high-dose groups (300 mg qd, 300 mg bid and 450 mg bid, orally). The first treatment cycle (21 days) was defined as the dose-limiting toxicity (DLT) assessment period. Patients could continue to receive ZG19018 until one of the treatment discontinuation criteria was met. Tumor response was assessed by the investigator per RECIST1.1 criteria. Pharmacokinetics profiles were also assessed in all pts. Results: As of January 31st, 2023, 14 pts (8 males and 6 females) completed the DLT assessments, with a median age of 65 years. Of them, 11 (78.6%) were non-small cell lung cancer (NSCLC) pts, 2 (14.3%) with colorectal cancer (CRC), and 1 (7.1%) with cervical cancer (CESC); 12 pts (85.7%) had received ≥ 1 line of stand therapies and 2 pts (14.3%) had received ≥ 3 lines. The dose group of 450 mg bid was determined as the maximally administered dose, where 2 pts experienced a DLT (grade 3 γ-GGT elevation and grade 3 ALT elevation, respectively), therefore an additional dose group of 400 mg bid has been added and is currently undergoing. Treatment-related adverse events (TRAEs) occurred in 13 pts (92.9%), most frequent in nausea (42.9%), diarrhea (42.9%), vomiting (35.7%), AST elevation (35.7%), γ-GGT elevation (35.7%), ALT elevation (28.6%), hypertriglyceridemia (28.6%), blood creatine phosphokinase MB elevation (21.4%) and ALP elevation (21.4%). No SAE was reported. In 12 pts evaluated for the best overall responses, 2 (16.7%) had PR (1 NSCLC, 1 CRC), 6 (50%) had SD (4 NSCLC, 1 CRC，1 CESC) and 4 (33.3%) had PD (4 NSCLC). The maximum drug exposure of ZG19018 is 8 months in 1 patient with colorectal cancer who is SD and remaining in the study. The C max and AUC 0-t increased from 50 mg qd to 450 mg bid approximately in dose proportion. Conclusions: ZG19018 is tolerable and demonstrates a good safety under the dose level of 450 mg bid. It also demonstrates preliminary antitumor effects in pts with solid tumors, with reasonable PK profiles. Clinical trial information: ChiCTR20220296 .
Vascular smooth muscle cells specific deletion of angiopoietin-like protein 8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy
Authors: Xiaolu Jiao, Huahui Yu, Zhiyong Du, Linyi Li, Chaowei Hu, Yunhui Du, Jing Zhang, Xiaoping Zhang, Qianwen Lv, Fan Li, Qiuju Sun, Yu Wang, Yanwen Qin
Journal: Cardiovascular Research (2023)

Abstract Aims Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 concentrations are increased in patients with hypertension and positively associated with blood pressure. ANGPTL8 deficiency ameliorates blood pressure in mice treated with chronic intermittent hypoxia. Currently, little is known regarding the pathophysiological role of the vascular smooth muscle cell (VSMC)-derived ANGPTL8 in hypertension and hypertensive cardiovascular remodelling. Methods and results Circulating ANGPTL8 concentrations, as determined by enzyme-linked immunosorbent assay, were significantly higher in hypertensive patients than in controls (524.51 ± 26.97 vs. 962.92 ± 15.91 pg/mL; P &amp;lt; 0.001). In hypertensive mice [angiotensin II (AngII) treatment for 14 days] and spontaneously hypertensive rats, ANGPTL8 expression was increased and predominantly located in VSMCs. In AngII-treated mice, systolic and diastolic blood pressure in Tagln-Cre-ANGPTL8fl/fl mice were approximately 15–25 mmHg lower than that in ANGPTL8fl/fl mice. AngII-induced vascular remodelling, vascular constriction, and increased expression of cell markers of proliferation (PCNA and Ki67) and migration (MMP-2 and MMP-9) were strikingly attenuated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. Furthermore, the AngII-induced increase in the heart size, heart weight, heart/body weight ratio, cardiomyocyte cross-sectional area, and collagen deposition was ameliorated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. In rat artery smooth muscle cells, ANGPTL8-short hairpin RNA decreased intracellular calcium levels and prevented AngII-induced proliferation and migration through the PI3K-Akt pathway, as shown using LY294002 (inhibitor of PI3K) and Akt inhibitor VIII. Conclusion This study suggests that ANGPTL8 in VSMCs plays an important role in AngII-induced hypertension and associated cardiovascular remodelling. ANGPTL8 may be a novel therapeutic target against pathological hypertension and hypertensive cardiovascular hypertrophy.
Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD
Authors: Thomas Marjot, Jeremy W Tomlinson, Leanne Hodson, David W Ray
Journal: Gut (2023)

Non-alcoholic fatty liver disease (NAFLD) represents a major public health concern and is associated with a substantial global burden of liver-related and cardiovascular-related morbidity and mortality. High total energy intake coupled with unhealthy consumption of ultra-processed foods and saturated fats have long been regarded as major dietary drivers of NAFLD. However, there is an accumulating body of evidence demonstrating that the timing of energy intake across a the day is also an important determinant of individual risk for NAFLD and associated metabolic conditions. This review summarises the available observational and epidemiological data describing associations between eating patterns and metabolic disease, including the negative effects of irregular meal patterns, skipping breakfast and night-time eating on liver health. We suggest that that these harmful behaviours deserve greater consideration in the risk stratification and management of patients with NAFLD particularly in a 24-hour society with continuous availability of food and with up to 20% of the population now engaged in shiftwork with mistimed eating patterns. We also draw on studies reporting the liver-specific impact of Ramadan, which represents a unique real-world opportunity to explore the physiological impact of fasting. By highlighting data from preclinical and pilot human studies, we present a further biological rationale for manipulating timing of energy intake to improve metabolic health and discuss how this may be mediated through restoration of natural circadian rhythms. Lastly, we comprehensively review the landscape of human trials of intermittent fasting and time-restricted eating in metabolic disease and offer a look to the future about how these dietary strategies may benefit patients with NAFLD and non-alcoholic steatohepatitis.
Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases
Authors: Chih Hung Lo, Jialiu Zeng
Journal: Translational Neurodegeneration (2023)

Lysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Multiple genetic factors have been linked to lysosomal de-acidification through impairing the vacuolar-type ATPase and ion channels on the organelle membrane. Similar lysosomal abnormalities are also present in sporadic forms of neurodegeneration, although the underlying pathogenic mechanisms are unclear and remain to be investigated. Importantly, recent studies have revealed early occurrence of lysosomal acidification impairment before the onset of neurodegeneration and late-stage pathology. However, there is a lack of methods for organelle pH monitoring in vivo and a dearth of lysosome-acidifying therapeutic agents. Here, we summarize and present evidence for the notion of defective lysosomal acidification as an early indicator of neurodegeneration and urge the critical need for technological advancement in developing tools for lysosomal pH monitoring and detection both in vivo and for clinical applications. We further discuss current preclinical pharmacological agents that modulate lysosomal acidification, including small molecules and nanomedicine, and their potential clinical translation into lysosome-targeting therapies. Both timely detection of lysosomal dysfunction and development of therapeutics that restore lysosomal function represent paradigm shifts in targeting neurodegenerative diseases.
Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17)
Authors: Ranjit Mohan Anjana, Ranjit Unnikrishnan, Mohan Deepa, Rajendra Pradeepa, Nikhil Tandon, Ashok Kumar Das, Shashank Joshi, Sarita Bajaj, Puthiyaveettil Kottayam Jabbar, Hiranya Kumar Das, Ajay Kumar, Vinay Kumar Dhandhania, Anil Bhansali, Paturi Vishnupriya Rao, Ankush Desai, Sanjay Kalra, Arvind Gupta, Ramakrishnan Lakshmy, Sri Venkata Madhu, Nirmal Elangovan, Subhankar Chowdhury, Ulagamathesan Venkatesan, Radhakrishnan Subashini, Tanvir Kaur, Rupinder Singh Dhaliwal, Viswanathan Mohan, Viswanathan Mohan, Ranjit Mohan Anjana, Ranjit Unnikrishnan, Rajendra Pradeepa, Mohan Deepa, Vasudevan Sudha, Elangovan Nirmal, Radhakrishnan Subashini, Ulagamathesan Venkatesan, L M Nath, Ramakrishnan Lakshmy, Nikhil Tandon, Jagadish Mahanta, Sri Venkata Madhu, Ashok Kumar Das, Arvind Pandey, Rupinder Singh Dhaliwal, Tanvir Kaur, Paturi Vishnupriya Rao, Modugu Nageswara Rao, Lobsang Jampa, T Kaki, Hiranya Kumar Das, Prasanta Kumar Borah, Ajay Kumar, Smita Sharma, Anil Bhansali, Kalpana Dash, Vijay Kumar Shrivas, Anand Krishnan, Ankush Desai, Amit Dias, Banshi Saboo, Jayendrasinh M Padhiyar, Sanjay Kalra, Bharti Kalra, Jatinder Kumar Mokta, Ramesh Gulepa, Vinay Kumar Dhandhania, Prabha Adhikari, Satish Rao, Puthiyaveettil Kottayam Jabbar, C Jayakumari, Sunil M Jain, Gaurav Gupta, Shashank Joshi, Chittaranjan S Yajnik, Prashant P Joshi, Somorjit Ningombam, T B Singh, R O Budnah, M R Basaiawmoit, None Rosangluaia, P C Lalramenga, Vizolie Suokhrie, Sao Tunyi, Saroj Kumar Tripathy, Nirmal Chandra Sahu, Anil Jacob Purty, Mary John, Arvind Gupta, B Lal Gupta, Sandeep K Shrivastava, Karma Jigme Tobgay, Tempo Tsewang Kaleon, Taranga Reang, Swapan Kumar Das, Sarita Bajaj, Manoj Kumar Mathur, Sagar Modi, Rakesh Kakkar, Subhankar Chowdhury, Sujoy Ghosh
Journal: The Lancet Diabetes & Endocrinology (2023)
A phase 1/2, first-in-human trial of ZB131, a novel antibody targeting cancer-specific plectin (CSP) in advanced solid tumors.
Authors: David Sommerhalder, Sarina A. Piha-Paul, Meredith Pelster, Mitesh J. Borad, Andrae Lavon Vandross, Alexander I. Spira, Samantha Perez, Lindsey Brinton, Kimberly Kelly, Ramesh K. Ramanathan, Matthew Reilley
Journal: Journal of Clinical Oncology (2023)

3083 Background: Cancer-Specific Plectin (CSP) is a novel pro-tumorigenic target that is selectively expressed on the surface of tumors, while absent from benign tissue. CSP is highly expressed in many solid cancers, particularly pancreatic (PC), cholangiocarcinoma (CCA), and ovarian (OC). ZB131 (Zielbio), is a humanized anti-CSP IgG1 monoclonal antibody that binds specifically to CSP on the surface of tumor cells, rapidly internalizes and modulates key proliferative and cytoskeletal remodeling signaling pathways to decrease cancer cell growth and increase the recruitment of anti-tumor immune infiltrates. Methods: The dose escalation (3+3 design) and expansion are enrolling adult patients (pts) with advanced treatment-refractory solid tumors. ZB131 was administered IV over 60 minutes (without premedication) weekly. The starting dose of ZB131 is 0.3 mg/kg followed by 1,3, 9, 15 and 30 mg/kg. Primary objectives are safety, tolerability, and maximum tolerated dose/determination of Phase 2 dose. Secondary objectives are preliminary efficacy (RECIST v1.1), Pharmacokinetic (PK) and pharmacodynamic parameters in blood and paired tumor biopsies. Results: As of 31 Jan 2023, 24 pts had enrolled (9 PC, 6 CCA, 4 OC, 5 other). The median age was 59.5 yr (range, 35 – 84) with a median of 4 prior lines of therapy. The median ZB131 treatment duration is 5.3 weeks (range, 1 – 33). No dose-limiting toxicities were observed up to the dose of 30 mg/kg which is currently enrolling. Treatment-related adverse events (TRAEs) were grade 1/ 2: nausea (n=6), fatigue (n=5), anemia (n=3), diarrhea (n=2), flulike symptoms (n=2), and vomiting (n=2). Mild flu-like symptoms and nausea/vomiting were observed during or following infusion at doses of 9 mg/kg and above. Except for one episode of Gr 3 neutropenia at the 30 mg/kg dose, no other drug-related grade 3/4 TRAE’s were reported. Five pts had stable disease range, 12 – 33 weeks (2 PC, 1 CCA, 2 OC), with a 43% decrease in CA-125 observed in one OC pt. The PKs are linear and dose-proportional for all dose levels evaluated (estimated T ½ of 6-9 days). No antidrug antibodies have been detected. Conclusions: Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472 .